Operations are currently controlled from Launch Complex 39, the location of the Vehicle Assembly Building. 6 km to the east of the assembly building are the two launch pads. 8 km south is the KSC Industrial Area, where many of the Center's support facilities are located and the administrative headquarters.

The announcement of the lunar program led to an expansion of operations from the Cape to the adjacent Merritt Island. NASA began acquisition in 1962, taking title to 33,952 hectares by outright purchase and negotiating with the state of Florida for an additional 22,600 hectares. In July 1962 the site was named the Launch Operations Center. It was renamed the John F. Kennedy Space Center in December 1963, after the recently assassinated president John F. Kennedy.

The lunar project had three stages - Mercury, Gemini and Apollo. The objective of Mercury was to orbit and retrieve a manned Earth satellite. The project started in October 1957 using the Atlas ICBM as the base to carry the Mercury payload. but early testing used the Redstone rocket for a series of suborbital flights including the 15-minute flights of Alan Shepard on May 5 and Virgil Grissom on July 21, 1961. The first human carried by an Atlas was John Glenn on February 20, 1962.

From the knowledge gained through Mercury the more complex two-man capsules of Gemini were prepared as was a new launcher based on the Titan II ICBM. The first manned flight took place on March 23, 1965 with John Young and Virgil Grissom. Gemini 4 featured the first extravehicular activity, by Edward H. White. There were twelve Gemini launches from KSC.

At KSC a $800 million massive new launch centre was built to take this new launcher - Launch Complex 39. It included a hanger to hold four Saturn V rockets, the Vehicle Assembly Building (VAB, 3.68 million m³); a transportation system from the hanger to the launch pad, capable of carrying 5440 tonnes; a 136 meter movable service structure and a control center. construction began in November 1962, the launch pads were completed by October 1965, the VAB was completed in June 1965, and the infrastucure by late 1966. From 1967 through 1973, there were 13 Saturn V launches from Complex 39.

Prior to the Saturn V launches there were a series of smaller Saturn I and IB launches to test the men and equipment from Complex 34 on the Cape Canaveral site. The death of three astronauts by fire on Apollo-Saturn 204 (later designated Apollo 1) on January 27, 1967 occurred at Complex 34.

The first Saturn V test launch, Apollo 4 (Apollo-Saturn 501) began its 104 hour countdown on October 30, 1967 and, after delays, was launched on November 9. Apollo 7 was the first manned test on October 11, 1968. Apollo 8 made 10 lunar orbits on December 24-25, 1968. Apollo 9 and Apollo 10 tested the lunar lander. Apollo 11 was launched on July 16, 1969 and the Moon was walked on at 10.56 pm, July 20. the Apollo program continued at KSC, through Apollo 14 (1971), the 24th American manned space flight (40th in the world), until Apollo 17 of December 1972.

ELV rocket development also continued at KSC, prior to Apollo a Atlas-Centaur launched from Launch Complex 36 had put the first American Surveyor softly on the Moon on May 30, 1966. A further five out of seven Surveyor craft were also successfully transferred to the Moon. From 1974-1977 the powerful Titan-Centaur became the new heavy lift vehicle for NASA, launching the Viking and Voyager series of spacecraft from Launch Complex 41, a Air Force site lent to NASA. Complex 41 later became the launch site for the most powerful unmanned U.S. rocket, the Titan IV, developed for the Air Force.

The Saturn V was also used to put Skylab 1 through 4 into orbit between 1970 and 1973.